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Aripiprazole in Psychosis Associated With Parkinson’s Disease

Received March 3, 2004; revised June 10, 2004; accepted June 15, 2004. From the Departments of Neurology and Neuropsychiatry, National Institute of Neurology and Neurosurgery of México. Address correspondence to Dr. López-Meza, Clinical Investigation Dept., National Institute of Neurology and Neurosurgery of México. Insurgentes sur 3877, Colonia la fama, Tlalpan, Mexico DF 14269; elmerlopez{at}hotmail.com (E-mail).

ABSTRACT

Aripiprazole is an agent for treating schizophrenia. The authors assume that aripiprazole as a dopamine receptor partial agonist may be useful in treating PD patients. Three cases are presented in this study. All patients were evaluated by the same clinician, a neuropsychiatrist well trained in the use of Brief Psychiatric Rating Scale (BPRS) and Clinical Global Impression (CGI). Aripiprazole was effective for reducing psychosis in each case.

Although motor symptoms are initial indicators of Parkinson’s disease (PD), the associated neuropsychiatric symptoms are what cause the greatest disability in advanced stages of the disease.¹ Psychosis, which may develop in PD (especially in elderly patients during dopaminergic therapy), is quite common, affecting approximately 25% of patients and is a serious public health problem.² Psychosis in PD patients is characterized mainly by the presence of visual hallucinations, formed by images of people, animals, and insects. However, auditory, tactile, and gustatory hallucinations may also occur. This may be accompanied by illusions and paranoid delusions, the latter being the most serious symptoms, leading to hospitalization and even suicide attempts.³ Traditional neuroleptics may ameliorate these mental features but concomitantly worsen the extrapyramidal manifestations.⁴ Managing psychosis is one of the most difficult challenges in the care of PD, and thus more treatments are required.⁵ Several antipsychotic agents have been proposed, including quetiapine, risperidone, olanzapine and clozapine.^1,2,4,6

Aripiprazole is an agent for treating schizophrenia that has a novel pharmacological profile.⁷ We assume that aripiprazole as a dopamine receptor partial agonist may be useful in treating PD patients. Two articles present the only available data on the use and outcome of aripiprazole in PD patients.^8,9 The first study reports on eight cases, with a starting dose of 5 mg to 10 mg per day and a slow increase over 3 to 7 days until side effects or improvement of psychosis occurred. Two patients experienced a good response, but six patients discontinued the treatment, and motor worsening occurred in two.⁸ Another case was reported recently⁹ and demonstrated a lack of therapeutic response and a considerable worsening of the motor components of disease, an adverse effect that could be related to reduction in L-dopa treatment and the use of high doses of aripiprazole (30 mg daily). In geriatric patients, doses generally used vary from 2 mg–15 mg daily, and the administration of 30 mg per day could be considered within the high range of therapeutic dosing in this particular population and thus could be related with a higher probability of adverse events.¹⁰

Efficacy, Safety, and Tolerability of Aripiprazole in Patients With Psychosis and PD Case 1
We report a 71-year-old male patient whose illness started when he was 66 years old. He complained of rigidity, tremors, and akinesia. His condition was studied and a PD diagnosis was made. Three years later, he developed memory impairment and psychosis. He was admitted in the emergency room because exacerbation of visual hallucinations occurred (Brief Psychiatric Rating Scale [BPRS] of 49 points and Clinical Global Impression [CGI] of 6), and aripiprazole was started at a dose of 15 mg per day while the patient was still receiving L-dopa, bromocriptine, and biperiden. These antiparkinsonian medications were maintained at the same dose. A four-week evaluation showed improvement of his symptoms, mainly visual hallucinations. During a 1 year follow-up, the patient’s symptoms were under control. In his most recent evaluation, he had an 18-point rating in BPRS, with CGI of 3. Neuroimaging, magnetic resonance imaging (MRI) and computerized axial tomography studies were normal for his age. We observed that the rigidity-akinesia-tremor syndrome did not increase and that the use of aripiprazole was well tolerated with no further adverse events.

Case 2
We present a 60-year-old man with parkinsonism as an initial symptom when he noted rest tremor in his right hand. Soon tremor appeared in his left hand as well. A diagnosis of PD was made, and L-dopa was prescribed. In 1998, he developed depressed mood. Four years later, he developed visual hallucinations and persecutory delusions. He was admitted to the neuropsychiatric service in order to receive electroconvulsive therapy (ECT), with a favorable recovery. Olanzapine was used at a 12.5 daily dose, with lack of response. Thus, we slowly switched medication to aripiprazole 15 mg per day. Simultaneously, the patient received L-dopa/carbidopa. We found a remarkable improvement in all of his psychotic symptoms. Brief Psychiatric Rating Scale decreased from 44 to 11 points, and CGI improved from 6 to 3 points. The follow-up time with the patient is 10 months, with a sustained significant remission of the psychotic symptoms. The motor symptoms remain steady.

Case 3
We report a 72-year-old female who started at age 65 with progressive rest tremor, rigidity, and bradykinesia. Benserazide/L-dopa was indicated after a PD diagnosis was determined. She was mentally healthy until age 69. At that time, she developed persecutory delusions and depressed mood. At age 71, she was admitted in the emergency room with visual and auditory hallucinations, persecutory delusions, and insomnia. Clozapine was initiated at a dose of 25 mg daily. Her outcome was characterized by a slow decrease of her psychotic symptoms. At age 73, she became psychotic, with visual hallucinations (BPRS of 40 and CGI of 4), and a switch in medication was made. We started aripiprazole, 15 mg per day, without making changes in previous medications (benserazide/L-dopa, venlafaxine and lorazepam). The patient showed decrease of her psychotic symptoms (mainly the visual hallucinations) and tolerability to the medication. These effects were sustained during a 4-month follow up. Brief Psychiatric Rating Scale decreased to 13 points, and her final CGI rating was 2.

All patients presented in these cases were evaluated by the same clinician, a neuropsychiatrist well trained in the use of BPRS and CGI scales.

We conclude that aripiprazole was effective for reducing psychosis in this 3-patient case series. The drug was well tolerated, with no reported adverse events. Controlled studies are needed to clarify the potential therapeutical role of aripiprazole in PD patients and to achieve a better understanding of the heterogeneity of results between previous reports^8,9 and our clinical observations.

REFERENCES

1. Juncos JL: Management of psychotic aspects of Parkinson’s disease. J Clin Psychiatry 1999; 60 Suppl 8:42–53
2. Wolters EC, Berendse HW: Management of psychosis in Parkinson’s disease. Curr Opin Neurol 2001; 14(4):499–504[CrossRef][Medline]
3. Factor SA, Feustel PJ, Friedman JH, et al: Parkinson Study Group. Longitudinal outcome of Parkinson’s disease patients with psychosis. Neurology 2003; 60(11):1756–1761[Abstract/Free Full Text]
4. Rabey JM, Treves TA, Neufeld MY, et al: Low-dose clozapine in the treatment of levodopa-induced mental disturbances in Parkinson’s disease. Neurology 1995; 45(3 Pt 1):432–434
5. Cummings JL: Managing psychosis in patients with Parkinson’s disease. N Engl J Med 1999; 340(10):801–803[Free Full Text]
6. Factor SA, Brown D, Molho ES, et al: Clozapine: a 2-year open trial in Parkinson’s disease patients with psychosis. Neurology 1994; 44(3):544–546
7. Potkin SG, Saha AR, Kujawa MJ, et al: Aripiprazole, an antipsychotic with a novel mechanism of action, and risperidone vs placebo in patients with schizophrenia and schizoaffective disorder. Arch Gen Psychiatry 2003; 60(7):681–690[Abstract/Free Full Text]
8. Fernandez HH, Trieschmann ME, Friedman JH: Aripiprazole for drug-induced psychosis in Parkinson disease: preliminary experience. Clin Neuropharmacol 2004; 27:4–5[Medline]
9. Schonfeldt-Lecuona C, Connemann BJ: Aripiprazole and Parkinson’s disease psychosis. Am J Psychiatry 2004; 161:373–374[Free Full Text]
10. Alexopoulos GS, Streim J, Carpenter D, et al: Expert Consensus Panel for Using Antipsychotic Drugs in Older Patients. J Clin Psychiatry 2004; 65 (suppl) 2:5–99; discussion 100–102; quiz 103–104

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